In-Hospital Dapagliflozin Speeds Decongestion in Heart Failure

Starting dapagliflozin (Farxiga; AstraZeneca) before a patient hospitalized for heart failure (HF) leaves the hospital produced measurable decongestion within a week, and those gains remained persistent through 2 months, according to a prespecified analysis of the DAPA ACT HF-TIMI 68 trial (NCT04363697). The data were presented as a late-breaking clinical trial at the European Society of Cardiology (ESC) Congress 2026 in Munich and published simultaneously in JACC: Heart Failure.^1,2

For pharmacists, the finding reinforces the case for initiating a sodium-glucose cotransporter 2 (SGLT2) inhibitor during the admission rather than deferring it to the outpatient setting.^1,2

What the Analysis Measured

DAPA ACT HF-TIMI 68 was a randomized, double-blind, placebo-controlled trial that enrolled 2401 patients hospitalized with a primary diagnosis of HF and elevated natriuretic peptide levels, randomly assigning them 1:1 to dapagliflozin 10 mg once daily or matching placebo after initial clinical stabilization. This prespecified secondary analysis assessed placebo-adjusted change from baseline in the modified EVEREST Composite Congestion Score (CCS)—summing orthopnea, peripheral edema, and jugular venous pressure—along with body weight, mean daily loop diuretic dose (expressed as furosemide 40 mg intravenous [IV] equivalents), and diuretic efficiency (weight loss per unit of loop diuretic) at 1 week, 1 month, and 2 months.^1,3

Early and Sustained Congestion Relief

Compared with placebo, dapagliflozin improved every decongestion end point by 1 week. The CCS fell by a least squares mean difference (LSMD) of −0.18 (95% CI, −0.33 to −0.04; P = .011), body weight dropped by −0.60 kg (95% CI, −0.95 to −0.26; P < .001), and mean daily loop diuretic dose declined by −0.12 furosemide 40 mg intravenous (IV) equivalents (95% CI, −0.22 to −0.02; P = .014). These improvements were sustained through 2 months.¹

Diuretic efficiency was the end point that kept moving. The benefit measured −0.93 kg per furosemide 40 mg IV equivalent at 1 week (95% CI, −1.61 to −0.25; P = .008) and progressively widened to −1.99 kg per equivalent by 2 months (95% CI, −3.19 to −0.78; P < .001). The authors noted that if the effect were driven solely by early natriuresis and osmotic diuresis, the curves would not be expected to keep diverging, suggesting benefits beyond direct diuretic augmentation.¹

Context With the Primary Trial

The decongestion signal sits alongside a neutral primary result. In the main DAPA ACT HF-TIMI 68 trial, in-hospital dapagliflozin did not significantly reduce the primary composite of cardiovascular death or worsening HF through 2 months. However, a prespecified meta-analysis pooling DAPA ACT HF-TIMI 68 with 2 other in-hospital SGLT2 inhibitor trials found that this strategy reduced the early risk of cardiovascular death or worsening HF and of all-cause mortality. Importantly, baseline congestion severity did not modify the treatment effect, so the authors concluded congestion severity should not be used to decide who gets an SGLT2 inhibitor among otherwise eligible patients.^1,3

Counseling and Monitoring Points

Dapagliflozin's established HF role spans reduced and preserved ejection fraction, and it is now a foundational pillar of guideline-directed medical therapy. Pharmacists supporting inpatient initiation can reinforce that the decongestive effect appeared consistent regardless of baseline ejection fraction or baseline loop diuretic dose. The authors also flagged that change in body weight is an imperfect surrogate for fluid loss with SGLT2 inhibitors, given the modest net calorie deficit from glycosuria—a useful caveat when counseling patients on expected weight changes. Standard monitoring for volume status, renal function, and symptomatic hypotension during initiation remains relevant.^1,4

Beyond SGLT2 inhibitors, the broader cardio-renal-metabolic toolkit continues to expand—and finerenone (Kerendia; Bayer), a nonsteroidal mineralocorticoid receptor antagonist, has carved out its own place in the treatment landscape. Approved for patients with chronic kidney disease associated with type 2 diabetes and, more recently, for HF with an ejection fraction of 40% or more, finerenone gives pharmacists another guideline-supported option for patients whose risk is not fully addressed by SGLT2 inhibition alone.⁵

As these agents increasingly stack in combination, the pharmacist's role in monitoring potassium and renal function—and in sequencing initiation to limit hypotension and hyperkalemia—becomes central to getting patients safely onto multiple pillars of therapy.

REFERENCES

1. Small AM, Patel SM, Thomas C, et al. Effect of in-hospital initiation of dapagliflozin on decongestion in patients hospitalized for heart failure: an analysis of the DAPA ACT HF-TIMI 68 trial. JACC Heart Fail. 2026;103366. doi 10.1016/j.jchf.2026.103366

2. Dapagliflozin and Effect on Cardiovascular Events in Acute Heart Failure -Thrombolysis in Myocardial Infarction 68 (DAPA ACT HF-TIMI 68). ClinicalTrials.gov Identifier: NCT04363697. Last Updated June 16, 2026. Accessed September 9, 2026. https://clinicaltrials.gov/study/NCT04363697

3. Berg DD, Patel SM, Haller PM, et al; DAPA ACT HF-TIMI 68 Trial Committees and Investigators. Dapagliflozin in patients hospitalized for heart failure: primary results of the DAPA ACT HF-TIMI 68 randomized clinical trial and meta-analysis of sodium-glucose cotransporter-2 inhibitors in patients hospitalized for heart failure. Circulation. 2025;152(20):1411-1422. doi:10.1161/CIRCULATIONAHA.125.076575

4. Abbey-Mott C. Clinical overview: dapagliflozin for patients with heart failure, reduced ejection fraction and preserved ejection fraction. Pharmacy Times. June 2, 2023. Accessed September 8, 2026. https://www.pharmacytimes.com/view/clinical-overview-dapagliflozin-for-patients-with-heart-failure-reduced-ejection-fraction-and-preserved-ejection-fraction

5. Halpern L. Finerenone approved by FDA for treatment of adults with heart failure. Pharmacy Times. July 14, 2025. Accessed September 9, 2026. https://www.pharmacytimes.com/view/finerenone-approved-by-fda-for-treatment-of-adults-with-heart-failure